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Chemistry of Unique Chiral Olefins. 4. Theoretical Studies of the Racemization Mechanism of trans- and cis-1,1′,2,2′,3,3′,4,4′-Octahydro-4,4′-biphenanthrylidenes Robert W. J. Zijlstra,1a Wolter F. Jager,1a Ben de Lange,1a Piet Th. van Duijnen,1a Ben L. Feringa,*,1a Hitoshi Goto,1b Akira Saito,1b Nagatoshi Koumura,1b and Nobuyuki Harada*,1b Department of Organic and Molecular Inorganic Chemistry, Groningen Centre for Catalysis and Synthesis, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands, and Institute for Chemical Reaction Science, Tohoku University, 2-1-1 Katahira, Aoba, Sendai 980-8577, Japan Received December 4, 1998
The minimum energy conformations and racemization barriers for the chiral sterically overcrowded helical alkenes, trans- and cis-1,1′,2,2′,3,3′,4,4′-octahydro-4,4′-biphenanthrylidenes (1 and 2), are reported. The trans-1 and cis-2 isomers can each adapt three different conformations, (P,P) and (M,M) (an enantiomeric pair) and an achiral (P,M) meso form, of which only the chiral isomers were obtained by synthesis. The conformations and heats of formation of (M,M)-(E)-1, (P,M)-(E)-1, (M,M)-(Z)-2, and (P,M)-(Z)-2 isomers were determined by MOPAC AM1 calculations. The racemization process for both the trans- and cis- isomers is postulated to occur via the (P,M) isomers by two successive inversions of the cyclohexenyl ring; (M,M) T (P,M) T (P,P). The (M,M) f (P,M) and reverse (P,M) f (M,M) isomerizations were simulated by reaction path calculations, providing the molecular structure and the activation energy of the transition state for each isomerization. For each racemization process, the activation enthalpy (∆Hq) was calculated as 23.9 and 19.9 kcal mol-1 for trans-olefin 1 and cis-olefin 2, respectively. These values reasonably agree with the experimental values obtained by temperature-dependent circular dichroism, optical rotation, and 1H NMR magnetization transfer measurements: ∆Hq ) 24.6 and 20.8 kcal mol-1 for trans-olefin 1 and cisolefin 2, respectively. While the racemization of cis-isomer 2 is controlled by the steric interaction of H5 with C4′a and C4′b, the surprisingly high barrier for trans-olefin 1 is due to the severe steric interaction between H5 and H3′R and/or H3′β protons. Introduction Sterically overcrowded ethylenes have attracted considerable attention due to their intriguing conformational behavior as well as the thermo- and photochromic properties associated with several members of this class of compounds.2 The chirality of bistricyclic alkenes was studied by extensive 1H NMR investigations of disubstituted bifluorenylidenes,3a,b biacridanes,3c bixanthylidenes,3d and bianthrones3e and energy barriers (∆Gq) for their conformational interconversions, ranging from 12 to 22 kcal mol-1, have been reported. The enantioresolution of these alkenes was not achieved. Recently we reported the synthesis, resolution, and remarkable thermal stability toward racemization of thioxanthene-based bistricyclic alkenes4 and 1,2-benzoannulated bithioxanthylidenes.5 For these compounds racemization barriers up to ∆Gq ) to 28.6 kcal mol-1 have been determined. Employing flexible 1,2,3,4-tetrahydrophenanthrene or 1,2,3-trihydronaphtho[2,1-b]thiopyran units instead of a more rigid (1) (a) University of Groningen. (b) Tohoku University. (2) For a review, see: Sandstro¨m, J. In Topics in Stereochemistry; Allinger, N. L., Eliel, E. L., Wilen, S. H., Eds.; Wiley: New York, 1983; Vol 14, p 160-169. (3) (a) Gault, I. R.; Ollis, W. D.; Sutherland, I. O. J. Chem Soc., Chem. Commun. 1970, 269. (b) Wang, X.; Lu, T. Y. J. Org. Chem. 1989, 54, 263. (c) Agranat, I.; Tapuhi, Y. J. Am. Chem. Soc. 1978, 100, 5604. (d) Agranat, I.; Tapuhi, Y. J. Am. Chem. Soc. 1979, 101, 665. (e) Agranat, I.; Tapuhi, Y. J. Org. Chem. 1979, 44, 1941. (4) Jager, W. F.; de Lange, B.; Feringa, B. L. Tetrahedron Lett. 1992, 33, 2887. (5) Feringa, B. L.; Jager, W. F.; de Lange, B. Chem. Commun. 1993, 288.
linear tricyclic unit, stable enantiomers of photochemically bistable overcrowded alkenes could be synthesized. These molecules are powerful building blocks for so-called chiroptical molecular switches.6 Detailed knowledge of the dynamic behavior of these chiral overcrowded ethylenes is of prime importance for their further development as new chiroptical materials. In the previous papers of this series, we reported the chemistry of trans- and cis-1,1′,2,2′,3,3′,4,4′-octahydro4,4′-biphenanthrylidenes 1 and 2 (Chart 1) as examples of inherently chiral olefins.7 Those compounds were the first examples where trans and cis isomers can independently be resolved into enantiomers.8 The relative structure of 1 and 2 were confirmed by X-ray analysis.7a,b,9 Inspection of molecular models indicates that the two (6) (a) Jager, W. F.; de Lange, B.; Feringa, B. L.; Meijer, E. W. J. Am. Chem. Soc. 1991, 113, 5468. (b) Huck, N. P. M.; Jager, W. F.; Feringa, B. L. Science 1996, 273, 1686. (c) Feringa, B. L.; Huck, N. P. M.; Schoevaars, A. M. Adv. Mater. 1996, 8, 681. (d) Jager, W. F.; de Jong, J. C.; de Lange, B.; Huck, N. P. M.; Meetsma, A.; Feringa, B. L. Angew. Chem., Int. Ed. Engl. 1995, 34, 348. (e) Feringa, B. L.; Huck, N. P. M.; van Doren, H. A. J. Am. Chem. Soc. 1995, 117, 9929. (7) (a) Part 1: Harada, N.; Saito, A.; Koumura, N.; Uda, H.; de Lange, B.; Jager, W. F.; Wynberg, H.; Feringa, B. L. J. Am. Chem. Soc. 1997, 119, 7241. (b) Part 2: Harada, N.; Saito, A.; Koumura, N.; Roe, D. C.; Jager, Zijlstra, R. W.; de Lange, B.; Feringa, B. L. J. Am. Chem. Soc. 1997, 119, 7249. (c) Part 3: Harada, N.; Koumura, N.; Feringa, B. L. J. Am. Chem. Soc. 1997, 119, 7256. (d) Harada, N.; Koumura, N.; Robillard, M. Enantiomer, 1997, 2, 303. (e) Koumura, N.; Harada, N. Enantiomer 1998, 3, 251. (8) Feringa, B. L.; Wynberg, H. J. Am. Chem. Soc. 1977, 99, 602. (9) Feringa, B. L.; Wynberg, H.; Duisenberg, A. J. M.; Spek, A. L. Recl. Trav. Chim., Pays-Bas. 1979, 98, 1.
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Chart 1
tetrahydrophenanthrene parts of these chiral olefins can adopt a helical structure. This means that, when constructing both trans-olefin 1 and cis-olefin 2, three different conformers can exist: (P,P) and (M,M) (an enantiomeric pair) and an achiral (P,M) meso form (Figure 1). We obtained both enantiomers of trans-olefin 1 and cis-olefin 2 in enantiopure forms and observed intense CD Cotton effects reflecting their strongly twisted π-electron systems.7a We have also succeeded in the theoretical determination of their absolute stereostructures by calculating CD spectra using the π-electron SCFCI-DV MO method.7a To prove their absolute stereochemistry, we synthesized enantiopure trans- and cis1,1′,2,2′,3,3′,4,4′-octahydro-3,3′-dimethyl-4,4′-biphenanthrylidenes 3 and 4 starting from (3R,4R)-(+)-1,2,3,4tetrahydro-3-methyl-4-phenanthrenol (Chart 1).7c The absolute configurations of chiral dimethyl olefins 3 and 4 were unambiguously determined by X-ray crystallography. Since the CD spectra of olefins 1 and 2 were similar in shape but opposite in sign to those of 3 and 4, respectively, the absolute stereostructures of chiral olefins 1 and 2 determined theoretically were proved in an experimental manner.7c During those studies, we observed the surprising phenomenon that cis-olefin 2 which looks more sterically hindered easily racemizes at room temperature without formation of trans-olefin 1; the racemization reaction was thermally accelerated and the activation enthalpy of racemization (∆Hq ) 20.8 ( 0.3 kcal mol-1 for cis-olefin 2) was determined.7b On the other hand, a significantly higher racemization barrier (∆Hq ) 24.6 ( 0.7 kcal mol-1) was obtained for trans-olefin 1, which appears sterically less hindered.7b These observations pose an intriguing mechanistic problem; how can the sterically more hindered cis-olefin 2 easily racemize at room temperature? Even when considering the fact that aromatic rings can show a large degree of flexibility as shown in a number of studies on chiral helicenes,10 it would be expected that the less hindered trans-olefin 1 is more likely to racemize (10) (a) Prinsen, W. J. C.; Laarhoven, W. H. In Topics in Current Chemistry; Vogtle, F., Weber, E., Eds.; Springer-Verlag: BerlinHeidelberg, 1984; p 125. (b) Martin, R. H. Angew. Chem. 1974, 86, 727.
Figure 1. Possible interconversion pathways between transolefin 1 and cis-isomer 2.
at room temperature, since the naphthyl units of 1 are on opposite sides of the molecule. To solve this challenging problem, we carried out theoretical calculations of molecular conformation and energy along the reaction pathway for racemization of chiral olefins 1 and 2. We report here the calculation results to clarify the reaction mechanism of their racemization. Recently, extensive conformational analyses of related dissymmetric aromatic hydrocarbons11 and overcrowded alkenes12 have been reported. These reported analyses, performed to find minimal energy conformations, were based on molecular mechanical calculations using MMP213 or semiempirical molecular orbital calculations such as AM1,14 PM3,15 and MNDO.16 Most calculations gave (11) (a) Rashidi-Ranjbar, P.; Sandstro¨m, J. J. Chem. Soc., Perkin Trans. 2. 1990, 901. (b) Agranat, I.; Cohen, S.; Isaksson, R.; Sandstro¨m, J.; Suissa, M. R. J. Org. Chem. 1990, 55, 4943. (12) (a) Lenoir, D.; Gano, J. E.; Park, B. S.; Pinkerton, A. A. J. Org. Chem. 1990, 55, 2688. (b) Bock, H.; Borrmann, H.; Havlas, Z.; Oberhammer, H.; Ruppert, K.; Simon, A. Angew. Chem., Int. Ed. Engl. 1991, 30, 1678. (c) Stezowski, J. J.; Biedermann, P. U.; Hildenbrand, T.; Dorsch, J. A.; Eckhardt, C. J.; Agranat, I. J. Chem. Soc., Chem. Commun, 1993, 213. (d) Badejo, I. T.; Karaman, R.; Pinkerton, A. A.; Fry, J. L. J. Org. Chem. 1990, 55, 4327. (13) (a) Allinger, N. L. QCPE program 395/400. Allinger Force Field Molecular Mechanics Calculations; Allinger, N. L., Ed.; Department of Chemistry, University of Georgia, Athens, GA 30602. (b) MM3. (14) (a) Dewar, M. J. S.; Zoebisch, E. G.; Healy, E. F.; Stewart, J. J. P. J. Am. Chem. Soc. 1985, 107, 3904. (b) Dewar, M. J. S.; Dieter, K. M. J. Am. Chem. Soc. 1986, 108, 8075. (c) Stewart, J. J. P. MOPAC93, Fujitsu Limited, Tokyo, 1993. (15) Stewart, J. P. P. J. Comput. Chem. 1989, 10, 209. (16) Dewar, M. J. S.; Thiel, W. J. Am. Chem. Soc. 1977, 99, 4899.
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accurate structures, consistent with experimental data obtained from 1H NMR spectra and X-ray analyses. In many cases the geometry and the relative enthalpy of formation ∆H(form) of the calculated minimum energy conformations could be used to assign NMR spectra of conformational mixtures and to understand geometrical interconversions between different geometrical isomers. In the studies described in this paper, we employed the AM1 semiempirical molecular orbital method to gain insight into the intriguing static and dynamic conformational behavior of compounds 1 and 2. Four minimum energy conformations, (M,M)-1, (P,M)-1, (M,M)-2, and (P,M)-2, were used as starting geometries for AM1-based reaction path calculations. The calculations simulate the racemization processes of 1 and 2. A detailed description of these processes, explaining the observed and calculated difference in thermal stability toward racemization of 1 and 2, is presented.
Setup of Calculations All possible minimum energy conformations of chiral transolefin 1 and cis isomer 2 were automatically generated by the CONFLEX-MM2 conformational space search17 and then fully optimized by the MOPAC93-AM1 method14 to reach a sufficiently small gradient norm (
